This proposal aims to examine the relationship between sleep architecture, particularly slow-wave sleep, and hypothalamic-pituitary-adrenal axis activity in chronic post-traumatic stress disorder (PTSD). We will study medication-free, non-substance-abusing male and female Vietnam-theater veterans with chronic PTSD with and without major depressive disorder (MDD). We will examine the effects of metyrapone, an antiglucocorticoid agent that enhances slow-wave sleep, on sleep architecture in PTSD subjects with and without MDD. Three groups, each consisting of male and female Vietnam veterans with a history of service in the Vietnam theater, will be studied: (1) Current combat-related PTSD and no lifetime history of MDD (N=60); (2) Current combat-related PTSD and current MDD (N=60); and (3) No lifetime PTSD or MDD (N=60). We will test whether differences in HPA activity contribute to the variability in sleep physiology in PTSD. The study will involve five nights of ambulatory polysomnography, two at home and three on the UCSF GCRC, where nocturnal cortisol activity will be measured and a metyrapone challenge will be performed. The sleep studies will be funded by an NIH grant. The study population includes the same subjects described in the GCRC protocol, "Magnetic Resonance Imaging and Spectroscopy of the Human Brain in Post-traumatic Stress Disorder" (Charles Marmar, M.D., Principal Investigator).